1.Phage/interleukin-4 liposome composite prevents relapse after maxillary expansion in mice
LI Ruizhi ; LIU Ruojing ; WANG Xingming ; PU Ximing ; YIN Xing ; ZOU Shujuan
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(6):529-540
Objective:
To explore the efficacy of a novel injectable hydrogel (GelMA/P11/IL4@LIP) loaded with P11 bacteriophages and interleukin-4 (IL-4) liposomes (LIP) in preventing relapse after maxillary expansion in mice, providing experimental evidence for its clinical application.
Methods:
This study was approved by the experimental animal ethics committee of our hospital. First, 15 7-week-old C57BL/6 mice were used to establish a maxillary expansion model and divided into 5 groups (3 mice in each group): a control group, post expansion day 3 group (PED3 group), post expansion day 7 group (PED7 group), retention for 14 days group (RET group), and relapse for 7 days group (REL group). The mice in each group were sacrificed at their designated time points (day 0, 3, 7, 21, 28), and their maxilla and anterior cranial regions were collected. Bone parameters and the inter-crestal distance (ICD) of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography (micro-CT). Histological staining was performed to evaluate bone formation and resorption, while immunohistochemistry (IHC) was performed for macrophage markers (CD86 and CD206), mesenchymal stem cell markers (glioma-associated oncogene homolog 1 [Gli1]), and osteogenic markers (Runt-related transcription factor 2 [Runx2] and Osterix [OSX]). Next, GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion. A total of 24 7-week-old C57BL/6 mice were divided into 4 groups (6 mice in each group): a blank control group, GelMA group, GelMA/P11 group, and GelMA/P11/IL4@LIP group. All mice underwent palatal expansion. On PED7, the expanders of all 24 mice were cemented with resin to initiate the 14-day retention period. On day 1 of the retention phase, the mice in each group received injections of saline, GelMA, GelMA/P11, or GelMA/P11/IL4@LIP at the midpalatal suture. After the 14-day retention period, three mice in each group were randomly selected and sacrificed, while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28 (REL). Micro-CT, histological staining, and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse.
Results:
The mice maxillary expansion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis (P = 0.008). IHC analysis demonstrated prolonged M1 macrophage infiltration, scarce Gli1+ mesenchymal stem cells, and insufficient expression of osteogenic markers (RUNX2 and OSX) (P < 0.001). Compared to the blank control and GelMA groups, GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL, promoted the timely M2 polarization of macrophages, recruited Gli1+ mesenchymal stem cells, and upregulated the expression of RUNX2 and OSX (P < 0.05).
Conclusion
The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages, as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture. The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polarization of macrophages, thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.
2.Expert consensus on clinical treatment of acute radiation syndrome from external irradiation
Li LIANG ; Long YUAN ; Changlin YU ; Qingjie LIU ; Yulong LIU ; Wenfeng YANG ; Jin WANG ; Weixu HUANG ; Ying LIU ; Cuiping LEI ; Huifang CHEN ; Ximing FU ; Baoshan CAO ; Mopei WANG ; Zhaohui ZHANG ; Yu XIAO ; Yamei CHEN ; Quanfu SUN
Chinese Journal of Radiological Medicine and Protection 2025;45(9):827-839
China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.
3.The value of coronary CT angiography-based traditional features and radiomics in identification of culprit plaques to cause acute myocardial infarction
Pei NIE ; Shuo ZHANG ; Yan DENG ; Shifeng YANG ; Xinxin YU ; Kaiyue ZHI ; He ZHU ; Peng LI ; Jingjing CUI ; Wenjing CHEN ; Yanmei WANG ; Yuchao XU ; Dapeng HAO ; Ximing WANG
Chinese Journal of Radiology 2025;59(9):1017-1028
Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.
4.Value of combined predictive model based on dual-layer detector spectral CT multiparametric radiomic features and quantitative parameters in preoperative diagnosis of gastric cancer serosal invasion
Huachun MA ; Qingguo DING ; Cen SHI ; Xinglu LI ; Wenbin SHEN ; Ximing WANG
Chinese Journal of Radiology 2025;59(9):1003-1010
Objective:To construct a combined prediction model based on dual-layer detector spectral CT radiomics features and quantitative parameters, and to evaluate its value in preoperative prediction of serosal invasion in gastric cancer.Methods:This case-control study retrospectively analyzed data from 253 gastric cancer patients confirmed by postoperative pathology at the First Affiliated Hospital of Soochow University (Center 1) and Changshu No.2 People′s Hospital (Center 2) from January 2022 to December 2023. Patients from Center 1 ( n=157) were randomly divided into training set ( n=110) and test set ( n=47) in a 7∶3 ratio, while patients from Center 2 ( n=96) served as an external validation set. Based on postoperative pathological serosal invasion status, patients were classified into serosal invasion group ( n=164) and non-serosal invasion group ( n=89), with distributions of 70/40, 30/17, and 64/32 in the training, test, and external validation sets, respectively. Spectral CT quantitative parameters, including arterial and venous phase iodine concentration (IC), normalized iodine concentration (NIC), arterial-venous IC differences, arterial-venous NIC differences (NIC pa), arterial enhancement fraction (AEF), and effective atomic number (Z eff), were measured. Radiomics features were extracted from venous-phase 40 keV monochromatic images. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature selection. The logistic regression classifier (LR-LASSO) was applied to construct the radiomics model. Univariate and multivariate logistic regression analyses identified independent risk factors for serosal invasion, including the radiomics signature (RadScore) and quantitative parameters. A clinical model was built using significant quantitative parameters, and a combined model integrated RadScore. An artificial model was based on cT4 staging assessed by two radiologists using venous-phase CT. The diagnostic performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). Results:A total of six radiomics features were selected to establish the radiomics model. RadScore ( OR=7.598, 95% CI 2.259-25.562, P=0.001) and NIC pa ( OR=4.598, 95% CI 1.404-15.050, P=0.012) served as independent risk factors. The NIC pa served as the clinical model. The AUCs (95% CI) of the combined model in the training, test, and external validation sets were 0.984 (0.969-1.000), 0.855 (0.728-0.982), and 0.773 (0.665-0.882), respectively. The AUCs of the artificial model were 0.741, 0.670, 0.644; of the clinical model were 0.709, 0.633, 0.626. The AUCs of the radiomics model were 0.963, 0.824, 0.741, respectively. Calibration curves showed good agreement between predicted probability and observed probability. The DCA confirmed higher clinical net benefits for the combined model. Conclusion:The combined model integrating dual-layer detector spectral CT radiomics features and quantitative parameters exhibits high efficacy for preoperative prediction of gastric cancer serosal invasion.
5.Correlation analysis between CT equipment and socio economic development situation in medical institutions of various grade and classification in Jiangsu province
Jiaming LU ; Qiming DENG ; Xiang LI ; Xin ZHANG ; Zhengge WANG ; Ming LI ; Ximing WANG ; Cheng LI ; Bing ZHANG ; Chunhong HU
China Medical Equipment 2025;22(3):97-101
Objective:To investigate the situation of computed tomography(CT)equipment and socio economic development of various grades and classifications of medical institutions in Jiangsu Province,and to analyze the interrelationship between them.Methods:From October 20,2023 to November 20,2023,a questionnaire survey was conducted on imported and domestic CT equipment of various grades and classifications of medical institutions in 13 prefecture-level cities in Jiangsu Province through online questionnaire survey of"questionnaire star".The gross domestic product(GDP)of each prefecture-level city in Jiangsu province was used as an indicator of measuring the level of socio-economic development in the region.The CT number,the row number of detector,quality of image,the total examination case number of daily average and the daily average case number of single machine examination of medical institutions of various grades and classifications of 13 prefecture-level cities were used to conduct correlation analysis with GDP values of various districts.Results:A total of 910 questionnaires were distributed,and 512 questionnaires were retrieved.There were 482 valid questionnaires in the 512 questionnaires,and the valid rate was 94.15,which involved to 482 various grade and classification institutions of 13 prefecture-level cities in Jiangsu province.The number of imported and domestic CT equipment in the 13 prefecture-level cities of Jiangsu Province positively correlated with the GDP of each city(r=0.882,0.880,P<0.001).The number of imported CT equipment with 64 rows and more than 64 rows,and with less than 64 rows,and the number of domestic CT equipment with 64 rows and more than 64 rows,and with less than 64 rows all positively correlated with the GDP of each city(r=0.880,0.881,0.736,0.897,P<0.05).The total number of daily average of examinations for imported and domestic CT equipment of 13 prefecture-level cities positively correlated with the GDP of each city(r=0.774,0.814,P<0.05).There were no significant difference in the image quality and the daily average case number of single machine examination between the domestic CT equipment and the imported CT equipment(P>0.05).Conclusion:The medical institutions of city with high level of economic development have more quantitative and more high-end CT equipment,and the quality of image of domestic CT equipment is equal to that of imported CT equipment regardless of the high and low level of economic development.
6.Epidemiological analysis of bloodstream isolates in hematology departments across Guangdong, 2020-2024
Yexin LIN ; Ximing CHEN ; Yan ZHANG ; Jiong WANG ; Wenwen LIANG ; Qinhong XIE ; Hualiang CHEN ; Qiuxue DENG ; Xu YANG ; Ningjing LIU ; Yijing WANG ; Mingxin LI ; Yangjin CHEN ; Yating ZHAO ; Nanhao HE ; Jiakang CHEN ; Shunian XIAO ; Chao ZHUO
Chinese Journal of Hematology 2025;46(6):521-529
Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.
7.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
8.Diagnostic value of multimodality-enhanced CT-based radiomics nomogram for muscle-invasive bladder urothelial carcinoma
Na LI ; Shifeng YANG ; Fei GAO ; Hexiang WANG ; Jia GUO ; Ximing WANG
Journal of Practical Radiology 2025;41(5):790-794
Objective To investigate the diagnostic value of multimodality-enhanced CT-based radiomics nomogram for muscle-inva-sive bladder urothelial carcinoma.Methods A retrospective analysis was performed on the preoperative data of 644 patients with pathologically confirmed bladder urothelial carcinoma from three medical centers.Region of interest(ROI)were drawn on preopera-tive contrast-enhanced CT images,and radiomics features were extracted.Patients from medical center 1 were randomly divided into training set and internal validation set in a 7∶3 ratio,while patients from medical centers 2 and 3 were combined as an external val-idation set.The diagnostic performance of the models was evaluated using receiver operating characteristic(ROC)curve.Results In the external validation set,the area under the curve(AUC)for diagnosing muscle-invasive bladder urothelial carcinoma using the multi-phase fusion radiomics model was 0.861[95% confidence interval(CI)0.811-0.911].The nomogram constructed by combi-ning the multi-phase fusion radiomics model with clinical factors achieved an AUC of 0.901(95% CI 0.862-0.939).Conclusion The nomogram combining multimodality-enhanced CT-based radiomics with clinical factors can effectively diagnose muscle-invasive bladder urothelial carcinoma.
9.Research progress on the mechanism of low-density lipoprotein transendothelial transport
Shuzhan ZHAO ; Dongxia JIN ; Ximing LI ; Tianxu HAO ; Yibei LU
Tianjin Medical Journal 2025;53(10):1110-1115
The transendothelial transport of low-density lipoprotein(LDL)and its subendothelial accumulation represent a central pathogenic mechanism in atherogenesis.This process involves a variety of receptors and molecular mechanisms that work together to regulate the transport of LDL in endothelial cells and its accumulation in blood vessel wall.In addition to receptor-mediated transport mechanisms,physiological and pathological factors such as hormones,inflammatory mediators and metabolites also play an important role in it.Recent studies have further elucidated the critical regulatory roles of these factors in LDL transendothelial transport,suggesting that targeting LDL transcytosis may represent an effective strategy for the prevention of early atherosclerosis and the treatment of related vascular diseases.This review summarizes recent advances in this field and discusses their potential clinical applications.
10.Effects and model evaluation of Jianpi Huatan formula on regulatory T cells and Th17 cells in polycystic ovary syndrome patients with spleen deficiency phlegm dampness syndrome
Yue DAI ; Bing HE ; Sijie YANG ; Ximing YU ; Zhengwang YANG ; Lan LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(9):1153-1164
AIM:To explore the effects of Jianpi Huatan formula on regulating T cells and helper T cells 17(Th17)cells in patients with polycystic ova-ry syndrome(PCOS)due to spleen deficiency and phlegm dampness syndrome,and conduct a model evaluation.METHODS:Ninety-two patients with spleen deficiency phlegm dampness syndrome(PCOS)admitted to our hospital from January 2023 to October 2024 were selected as the research sub-jects.Propensity score matching(PSM)method was used to match them in a 1:1 ratio,with 46 pa-tients in each group.The control group received conventional treatment,while the observation group received treatment with Jianpi Huatan for-mula on the basis of the control group.Compared and analyze the differences in clinical data and lab-oratory indicators between two groups;Compared the changes of sex hormone,glucose metabolism and TCM syndrome score before and after treat-ment in the two groups,and focused on the chang-es of regulatory T cells(Treg)and Th17 cells in the two groups before and after treatment;And used the Generalized Estimation Equation(GEE)model to analyze its improvement.Multiple linear regres-sion analysis was used to examine its correlation with the score of traditional Chinese medicine syn-drome.A time effect model of Jianpi Huatan formu-la for treating PCOS with spleen deficiency and phlegm dampness syndrome was established using a nonlinear mixed effects model.The fitting effect of the final model was evaluated through the good-ness of fit.Bootstrap was used to test and evaluate the stability of model parameters.Visual prediction testing was used to evaluate the predictive perfor-mance of the model.Typical time effect curves of traditional Chinese medicine symptom scores was simulated based on the final model for each base-line.RESULTS:After treatment,the total effective rate of the observation group was significantly high-er than that of the control group(χ2=4.842,P=0.028);Compared with before treatment,after 1months and 3 months of treatment,TC,TG,LDL-C,T,LH,FSH,AMH,FPG,FINS,HOMA-IR,the score of traditional Chinese medicine syndrome were sig-nificantly reduced,while E2 and HDL-C were signifi-cantly increased,and the improvement in the ob-servation group was significantly greater than that in the control group(P<0.05);The results of repeat-ed measures ANOVA showed significant difference-sin the time effects,inter group effects,and interac-tion effects of Treg,Th17,and Treg/Th17 between the two groups of patients(P<0.05).The GEE anal-ysis results showed that the improvement of Treg,Th17,and Treg/Th17 in the observation group were better than that in the control group(P<0.05);The results of multiple linear regression analysis showed that the levels of TC,TG,LDL-C,T,LH,FSH,AMH,FPG,FINS,HOMA-IR,Th17 were significantly positively correlated with TCM syndrome score,while the levels of E2,HDL-C,Treg,and Treg/Th17 were significantly negatively correlated with TCM syndrome score(P<0.05);The decrease in tradition-al Chinese medicine symptom score compared to baseline gradually increases over time,eventually reaching the pharmacological platform,which was consistent with the classic Emax model.After gradu-ally screening covariates,it was found that the baseline value of traditional Chinese medicine symptom score had a significant impact on the effi-cacy parameter Emax.The final model was Emax,i=15.42+1.21×(Baselinei-24.41).The goodness of fit results showed that the final model had a good fit-ting effect on the measured data.The model pa-rameters obtained from Bootstrap testing were very consistent with the original model,indicated that the model parameter estimation was robust.The visual prediction test results showed that the model had good predictive performance.The typi-cal efficacy time curve showed that the higher the baseline value of TCM symptom score,the greater the decrease in score.At 3 months of treatment,the TCM symptom score at each baseline basically decreased to below 10 points.CONCLUSION:The formula for strengthening the spleen and resolving phlegm can effectively improve the levels of Treg and Th17 in PCOS patients with spleen deficiency and phlegm dampness syndrome,and has good therapeutic effects,which is worthy of clinical appli-cation.


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